PROJECT SUMMARY The most common occupational and environmental hazard in this country is noise. It's not surprising, then, that noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit, behind only age-related hearing loss (presbycusis). Although therapeutics that target the free radical pathway have shown promise for reducing NIHL, there are no effective nutraceuticals or approved medications for NIHL. Development of an efficacious treatment has been hampered by the complex array of cellular and molecular pathways involved in NIHL. Our preliminary studies have shown that the Chinese herb Stephania tetrandra and its main extract, tetrandrine (TET), can effectively protect against NIHL in mice. Clinical use of this herb has exhibited an excellent long-term safety profile. Moreover, TET possesses strong antioxidant and anti-inflammatory properties, and can also block calcium channels, thus targeting three main signaling pathways that underlie NIHL. Consistent with the funding priorities at National Center for Complementary and Integrative Health, in this Phase I application, we will determine the median effective dose (ED50) for this herb extract to prevent (Aim 1) and treat (Aim 2) NIHL in rats using a long noise exposure model (8 hours per day) similar to most industrial working environments. The innovative aspects of our approach are: (1) developing a nutraceutical against NIHL, thus breaking a major access barrier for customers, who are more likely to visit audiologists for hearing treatment; (2) testing in a rat model with cumulative noise exposure similar to that encountered by factory workers; (3) selecting an herb with well-characterized pharmacological properties and a long safety history of clinical applications; and (4) targeting multiple signaling pathways that underlie NIHL. If the outcome of this study is successful, we will then obtain institutional review board (IRB) approval to conduct SBIR Phase II studies in humans of this nutraceutical against NIHL. The goal of our program is to bring this nutraceutical to market for use in the prevention and treatment of NIHL. If this approach is successful, similar nutraceuticals will be evaluated for potential prevention of presbycusis.